tbuckley/cabot-search huggingface dataset:
Highlights of This Issue
Journal: Clinical Cancer Research (2013)

The rarity of pediatric adrenocortical carcinoma (ACC) presents significant challenges in developing more effective treatment options. Pinto and colleagues report the establishment of the first validated xenograft for studying childhood ACC. They tested a panel of common chemotherapeutic drugs in this experimental model and identified topotecan as a new cytostatic agent in the context of this tumor type. Notably, a child with ACC that had been refractory to standard therapy responded to topotecan as a single agent. These findings show promise that topotecan may be effective in treating ACC, warranting further clinical investigation.The Aurora kinases are a family of serine/threonine kinases involved in the mitotic spindle checkpoint that have been found to be overexpressed in certain human cancers, including bladder cancer. In evaluating Aurora kinase A as a possible therapeutic target, Zhou and colleagues found that the Aurora kinase A inhibitor MLN8237 impairs cell viability and cell-cycle progression in human bladder cancer cells and exhibits antitumor activity in a mouse xenograft model of bladder cancer. This study identifies the Aurora kinases as potential drug targets in human bladder cancer.The genetic heterogeneity of glioblastoma represents a significant obstacle for developing effective targeted therapy. Cheng and colleagues show that pharmaceutical inhibition of proteins from the bromodomain and extraterminal domain (BET) family of epigenetic readers induces broad antineoplastic effects in glioblastoma tumors with different genetic backgrounds. They observed that these effects were mediated, at least in part, by widespread induction of CDKN1A and downregulation of BCL2L1. These results highlight the promise of emerging second-generation epigenetic drugs in complex solid tumors. Whether the BET bromodomain proteins represent an Achilles' heel for glioblastoma warrants further investigation.CD19 is an almost universal surface marker of B-cell precursor acute lymphoblastic leukemia (ALL). The novel antibody–drug conjugate SAR3419, currently in clinical trials against adult CD19-positive malignancies, delivers the maytansinoid DM4 drug to its target population with high specificity. Carol and colleagues show the high efficacy of SAR3419 as a single agent against CD19-positive pediatric ALL xenograft models and report that the extent of response was correlated with the level of CD19 expression. In their study, when SAR3419 was administered as protracted therapy after remission induction with a regimen of established drugs, the combination prevented leukemia relapse into hematopoietic and lymphoid organs. These results provide the basis to combine SAR3419 with established drugs in high-risk ALL as a means to improve treatment outcomes.
Conversion of pemphigoid gestationis to bullous pemphigoid- two refractory cases highlighting this association
Authors: R.E. JENKINS, S.A. VAUGHAN JONES, M.M. BLACK
Journal: British Journal of Dermatology (1996)

Summary Pemphigoid gestationis and bullous pemphigoid are autoimmune diseases characterized by subepidermal blisters and antibodies against the hemidesmosomal antigens: BPAGI and BPAG2. Clinical, histological and immunological similarities between pemphigoid gestationis and bullous pemphigoid suggest that they may have common pathogenetic determinants. We report two patients who presented initially with clinico-pathological features characteristic of pemphigold gestationis but who subsequently evolved into bullous pemphigold.
Epitheliomesenchymal Interactions in the Proliferative Response Evoked by Polyoma Virus in Odontogenic Epithelium &lt;italic&gt;In Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: J. H. P. Main, M. A. Waheed
Journal: JNCI Journal of the National Cancer Institute (1971)

In incisor tooth germs from 14-day mouse embryos infected with polyoma virus (PY) and grown in organ culture, the epithelium proliferated after about 28 days in vitro; the earliest examples were seen at 24 days. Transplants of these proliferating cultures have not yet resulted in the development of a neoplasm at the site of transfer. Uninfected tooth germs treated similarly did not show the epithelial proliferation. Trypsin-separated, odontogenic epithelium from 14-day mouse tooth germs did not survive in culture for more than 10 days, whether infected with PY or not. Odontogenic mesenchyme alone grew in culture with or without PY, infected cultures showing viral cytopathic changes. When fresh odontogenic epithelium was added to uninfected odontogenic mesenchyme maintained in vitro for about 28 days, some morphological and cytological induction was seen in the epithelium. When fresh epithelium or whole tooth germs were added to mesenchyme grown for about 28 days with PY, the epithelium proliferated after 10 days in vitro. The earlier proliferation seen in the delayed recombination cultures implies an inductive action by the mesenchyme.
Highlights of This Issue
Journal: Clinical Cancer Research (2012)

Tumor-infiltrating macrophages are potential independent indicators of poor outcome in classical Hodgkin lymphoma (cHL) in adults, but nothing is known in pediatric cases.In this study, Barros and colleagues investigated macrophages and dendritic cells in pediatric cHL, taking into account the Epstein-Barr virus (EBV) status of the Hodgkin and Reed-Sternberg cells and lymphocyte composition of the tumor microenvironment.The results show that macrophage composition in pediatric cHL is distinct from that of adult cHL and that the prognostic role of macrophages in pediatric cHL is affected by EBV status.
Isoniazid Hepatoxicity
Authors: ARTURO R. ROLLA
Journal: Annals of Internal Medicine (1974)

Comments and Corrections1 February 1974Isoniazid HepatoxicityARTURO R. ROLLA, M.D.ARTURO R. ROLLA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-2-278 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: With the letter of Alonso and Starke (Ann Intern Med79:752, 1973), 35 cases of isoniazidinduced hepatitis have been reported. I would like to call your attention to another possible case, reported by Perret, Hopf, and Frei as a case of spontaneous lactic acidosis (Helv Med Acta33:16-21, 1966). The patient was a 53-year-old man with a long history of tuberculosis. Several days after he was started on viomycin, Isoxyl (thiocarlide), and isoniazid the patient suddenly developed tachypnea and tachycardia. He was found to have lactic acidosis with an arterial pH of 7.15 and a plasma lactate... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New England Deaconess Hospital Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEvaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections 1 February 1974Volume 80, Issue 2Page: 278-279KeywordsBlood plasmaHepatitisIsoniazidLactatesLactic acidosisTachycardiaTachypnea Issue Published: 1 February 1974 PDF downloadLoading ...
Biochemical Properties of a Hamster Syncytium-Forming (“Foamy”) Virus&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: Jerome F. Hruska, Kenneth K. Takemoto
Journal: JNCI Journal of the National Cancer Institute (1975)

A hamster syncytium-forming (“foamy”) virus (HFV) was characterized. The HFV sedimented in isopyknic sucrose density gradients at 1.16–1.165 g/ml. It had RNA but no DNA, its replication was inhibited by actinomycin D, and it contained virion-associated, RNA-dependent DNA polymerase. Analysis of the RNA from purified virus showed several species: 62S, 40S, 28-30S, 18-205, and 4-7S.
A scanning electron microscopic study of liver microcirculation disarrangement in experimental rat cirrhosis
Authors: Eugenio Gaudio, Luigi Pannarale, Paolo Onori, Oliviero Riggio
Journal: Hepatology (1993)

Hepatic microcirculation has been related to liver function in several studies. The principle of this relationship lies in the sequential distribution of blood from the feeding vessels of the hepatic acinus to the central vein. This study was undertaken to investigate the progressive changes at different sites of the liver microvascular bed in the developing cirrhosis, both by light microscopy and scanning electron microscopy of corrosion casts. Experimental cirrhosis was induced with intragastric carbon tetrachloride. The most important vascular changes progressively observed are the reduction of the distance between the pre- and postsinusoidal vessels, the presence of newly formed shunting vessels bypassing the sinusoids and, finally, the development of a perinodular vascular plexus composed of pre- and postsinusoidal vessels. Newly formed vessels grow through preformed tissue septa. These vascular modifications make any zonal gradient hardly possible. The loss of the zonal gradient of perfusion could highly modify liver function, along with the structural changes of hepatic laminae. Hepatocyte regeneration cannot recover the original vascular relationships: this makes the morphological and functional destructuralization of cirrhotic liver irreversible. (HEPATOLOGY 1993;17:477–485.)
POS0124 DIAGNOSTIC VALUE OF LIVER STIFFNESS AS MARKER OF HEPATIC MARKER OF HEPATIC AMYLOID DEPOSITION IN SYSTEMIC AL AMYLOIDOSIS
Authors: A. F. Brunger, J. Bijzet, H. Blokzijl, R. Van Rheenen, R. Gans, B. Hazenberg, H. L. A. Nienhuis
Journal: Annals of the Rheumatic Diseases (2022)

Background Hepatic involvement in AL amyloidosis is often asymptomatic but does affect prognosis and should be taken into account during follow-up. An increased plasma level of alkaline phosphatase (ALP) or increased liver span are part of the conventional diagnostic criteria for establishing hepatic involvement 1 , however these markers are nonspecific. 123 I-labeled serum amyloid P component (SAP) scintigraphy is a specific and sensitive method to establish hepatic involvement but is not widely available. Liver stiffness measured by transient elastography is increased in AL amyloidosis patients with hepatic involvement and could be useful in establishing liver involvement and monitoring treatment response in AL-amyloidosis. Objectives To assess the diagnostic value of liver stiffness (LS) for liver involvement in AL amyloidosis and the utility of LS to monitor treatment effect using SAP scintigraphy as gold standard. Methods LS was measured prospectively in 49 treatment naive patients with systemic AL amyloidosis and 9 patients with wild type transthyretin amyloidosis (ATTRwt) with cardiomyopathy (cardiac controls). In addition, LS was longitudinally measured in 10 AL amyloidosis patients of whom 9 patients had liver involvement. SAP scintigraphy, laboratory assessments including ALP and measurement of liver span was performed in all patients. Results Of the 49 patients, 27 patients had liver involvement (of whom 24 also had heart involvement), 10 patients had heart involvement, 12 patients had no heart or liver involvement. Median LS was significantly higher in AL amyloidosis patients with liver involvement (22.8 kPa, range 4.3-75), than in AL amyloidosis patients without liver involvement (6.3 kPa, range 4.4-35.8) (p=0.000). Also a significant difference was seen between AL amyloidosis patients with liver involvement (22.8.9, range 4.3-75) versus, heart involvement (9.0, range 4.5-35.8) (p=0.02), no liver or heart involvement (5.7, range 4.4-10.1) (p=0.0001), and ATTRwt patients (9.9 kPa, range 4.0-14.6) (p=0.01). Furthermore, LS values seemed to significantly decrease over time in AL amyloidosis patients with liver involvement with a good hematologic response to treatment. Conclusion LS is a non-invasive tool which seems to be useful in clinical practice to establish liver involvement in patients with AL amyloidosis. In addition, it is a promising marker in the follow up of AL amyloidosis patients for establishing hepatic response over time. References [1]Gertz et al. Am J Hematol 2005;79319-328 Disclosure of Interests None declared
Spinal Cord Compression due to Extramedullary Hematopoiesis
Authors: Franklin Price
Journal: JAMA (1985)

MYELOFIBROSIS is not uncommon, but compression of the spinal cord due to extramedullary hematopoiesis in this condition is rare. Of the 11 cases of extramedullary hematopoiesis causing spinal cord compression in the spinal epidural space that have been reported in the literature, six were associated with myelofibrosis and five with thalassemia major.<sup>1-5</sup>We report the 12th case, which involved the successful treatment of a woman with longstanding myelofibrosis, who underwent surgical decompression followed by radiation treatment for this condition. <h3>Report of a Case</h3> A 74-year-old woman was diagnosed as having myelofibrosis by the results of a bone marrow biopsy in January 1981. Initial treatment with oxymetholone and folic acid was continued until April 1983, at which time prednisone was added because of persistent hemoglobin values of about 5 g/dL. On repeated office visits thereafter, the hemoglobin values were about 10 g/dL. There was no objective evidence of blood loss.
Highlights of This Issue
Journal: Clinical Cancer Research (2015)

Whatcott and colleagues examined extracellular matrix deposition in clinical samples of both primary pancreatic tumors and metastases from various sites. Looking at collagen I levels, they observed that primary tumors and metastatic lesions show comparable levels of desmoplasia. They also report a negative correlation between patient survival and extracellular matrix (Collagen I or Hyaluronan) deposition. As stromal targeting is emerging as an alternative approach to enhance chemotherapeutic interventions, their analysis provides further support for use of the approach, even in patients with late stage, metastatic disease.In follicular lymphoma, the tumor microenvironment has been shown to influence patient outcomes. To clarify the association of tumor-associated macrophages (TAMs) with prognosis, Kridel and colleagues performed immunohistochemistry for CD163 in two large patient cohorts. In cases from British Columbia who had been treated with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), CD163+, macrophages were associated with poor prognosis, but an opposite outcome correlation was observed in those patients from the PRIMA trial who received an anthracycline in addition to R-CVP (R-CHOP). These data show that the prognostic impact of TAMs is highly dependent on patient characteristics and/or treatment received.Glycodelin, an immunomodulatory protein, is highly expressed during the menstruation cycle and pregnancy. In the current study, Schneider and colleagues demonstrated a high expression of glycodelin in NSCLC. A knockdown of glycodelin mRNA resulted in a deregulation of immune system modulatory proteins, such as PDL1/PDL2 and MICA/MICB, and a reduced migration of NSCLC cell lines. Glycodelin was secreted from NSCLC tumors and could be measured in patients' serum. Furthermore, the serum levels correlated with the tumor response to therapy and therefore demonstrated that glycodelin can be used as a helpful follow-up biomarker.The prevalence of a pretreatment EGFR T790M mutation in patients with EGFR-mutant non-small cell lung cancer (NSCLC) remains unclear. To assess this question, and its clinical significance, Watanabe and colleagues used an ultra-sensitive droplet digital PCR technique. Surgically resected tumor tissues from 373 early-stage NSCLC patients with EGFR-activating mutations were examined, and the overall incidence of the pretreatment EGFR T790M mutation was 79.9% (298/373). The mutant allele frequency ranged from 0.009% to 26.9%. These data suggest that an ultra-sensitive method can provide high resolution mutational profiling, and open up the possibility of developing new treatment strategies with EGFR-TKIs, including third-generation TKIs for patients with EGFR-mutant NSCLC.
Long-term Use of Nicotine Chewing Gum
Authors: Peter Hajek
Journal: JAMA (1988)

Among 538 clients of a Smokers Clinic who were treated with 2-mg nicotine chewing gum, 34 (6.3%) were still using the gum at one-year follow-up. This group represented 25% of lapse-free abstainers. At one-year follow-up, long-term gum users were using an average of 6.8 pieces of gum per day. Long-term gum users were similar to treatment failures in cigarette consumption and tobacco dependence, while "gum-free" successes were significantly lighter and less-dependent smokers. Long-term gum users used more gum during the four weeks of treatment than treatment failures, who in turn used more than the gum-free successes. It is suggested that for many the long-term use of gum was an essential ingredient of their success. Long-term gum users gained significantly less weight than other long-term treatment successes. (<i>JAMA</i>1988;260:1593-1596)
Developmental Pattern of 3-Methylcholanthrene-Inducible Mutagenic Activation of &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide, 2-Fluorenamine, and 2,4-Diaminoanisole in the Rabbit&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Tore Aune, Erik Dybing
 5, Snorri S. Thorgeirsson
Journal: JNCI Journal of the National Cancer Institute (1980)

The effects of 3-methylcholanthrene (MCA) on mutagenic activation of the carcinogenic arylamines N-2-fluorenylacetamide (FAA), 2-fluorenamine (FA), and 2,4-diaminoanisole (2,4-DAA) by liver homogenates were studied postnatally in Dutch rabbits. These effects were compared with the developmental profiles of cytochrome P448 and aryl hydrocarbon hydroxylase (AHH) activity. Mutagenic activation of FA and 2,4-DAA was increased by MCA as early as 2 days after birth, whereas induction of FAA mutagenicity appeared 6 days after birth. Thereafter, induction of all three arylamines closely paralleled induction of cytochrome P448, which was maintained into adulthood. In contrast, induction of AHH activity by MCA was highest at 2 days of age and decreased to control levels 20 days after birth.
Group Psychotherapy for Sexual Maladjustments
Authors: SAMUEL B. HADDEN
Journal: American Journal of Psychiatry (1968)

On the basis of his own experience and the reports of other therapists, this author concludes that group therapy is a sound approach to the treatment of sexual maladjustment. The group provides realistic and constructive criticism for each of its members, along with support that is conditional upon the individual's efforts to change. The authority of such a peer group does not activate the hostility often encountered by therapists in a one-to-one relationship with similar patients.
Postemetic Rupture of Herniated Cardia of the Stomach
Authors: Gregory A. Gapp
Journal: JAMA (1982)

THE CLASSIC description of postemetic or spontaneous rupture of the esophagus was recorded by a distinguished Dutch physician, Herman Boerhaave, in 1724.<sup>1</sup>His patient, the Grand Admiral Baron van Wassenauer, experienced intense chest pain during induced vomiting at the conclusion of an eating and drinking episode. His general condition deteriorated rapidly and he died 18 hours later. At postmortem examination, Boerhaave found a rent in the lower third of the esophagus with a large quantity of gastric contents and air in the mediastinum and pleural cavity. In postemetic rupture of the esophagus, the perforation almost always occurs in the lower third, and in 90% of patients it is located posterolaterally on the left side. The etiology remains enigmatic, but it is conjectured that the extension of smoothmuscle fibers from the esophagus onto the stomach wall results in a defective or weakened muscular zone. The insufflation of air into the
Controlling the Tuberculosis Epidemic: The Analogy With Mental Illness-Reply
Authors: Lawrence O. Gostin
Journal: JAMA (1993)

<h3>In Reply.</h3> —I am grateful to Dr Cowen for explaining many of the differences and similarities between TB and mental illness in assessing the need for compulsory detention and treatment. To be sure, the analogy between mental illness and TB control is imperfect. Yet, my proposal for adopting many of the standards and procedures used in mental illness for use in TB control warrants serious consideration. Confinement under civil law of persons who have not committed a criminal offense is highly unusual in our constitutional society. We do so only on the grounds that the individual poses danger to self or others. At present, persons with mental illness or contagious TB are virtually the only populations in society subject to civil commitment. The law, therefore, clearly treats persons with mental illness and TB in comparable ways. The differences between TB and mental illness only reinforce the observation that TB is
Myocardial reoxygenation damage: can it be circumvented?
Authors: S P CHAPPELL, M J LEWIS, A H HENDERSON
Journal: Cardiovascular Research (1985)

Journal Article Myocardial reoxygenation damage: can it be circumvented? Get access S P CHAPPELL, S P CHAPPELL From the Departments of Cardiology and Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff Search for other works by this author on: Oxford Academic PubMed Google Scholar M J LEWIS, M J LEWIS * From the Departments of Cardiology and Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff *Address for correspondence and reprint requests: Dr M J Lewis, Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN. Search for other works by this author on: Oxford Academic PubMed Google Scholar A H HENDERSON A H HENDERSON From the Departments of Cardiology and Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 19, Issue 5, May 1985, Pages 299–303, https://doi.org/10.1093/cvr/19.5.299 Published: 01 May 1985
An Agenda for Research in Medical Education
Authors: Paul J. Sanazaro
Journal: JAMA (1966)

The 1960's stand recorded as the decade in which national goals for American society became inseparable from national goals for medicine and medical education. Federal legislation has established equal access of all citizens to the full benefits of modern health care as a basic social right. Equal access is to be promoted by removal of economic and social barriers, by innovations in the delivery of health services, and by increasing the numbers of health care personnel. What was before a philosophical view has become a guiding principle: medical education must be consciously directed to meeting the medical care needs and demands of society on the local, regional, and national levels. Far reaching decisions will be made, and quickly, because the combination of money and mandate is uniquely persuasive. However, medical schools cannot fully adapt in one spasm of pragmatic decisions. Their capacity to respond is limited in part by the